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Kruppel-like transcription factor 13 regulates T lymphocyte survival in vivo. J Immunol 2007 May 01;178(9):5496-504

Date

04/20/2007

Pubmed ID

17442931

Pubmed Central ID

PMC2664650

DOI

10.4049/jimmunol.178.9.5496

Scopus ID

2-s2.0-34247557502   43 Citations

Abstract

Krüppel-like transcription factor (KLF)13, previously shown to regulate RANTES expression in vitro, is a member of the Krüppel- like family of transcription factors that controls many growth and developmental processes. To ascertain the function of KLF13 in vivo, Klf13-deficient mice were generated by gene targeting. As expected, activated T lymphocytes from Klf13(-/-) mice show decreased RANTES expression. However, these mice also exhibit enlarged thymi and spleens. TUNEL, as well as spontaneous and activation-induced death assays, demonstrated that prolonged survival of Klf13(-/-) thymocytes was due to decreased apoptosis. Microarray analysis suggests that protection from apoptosis-inducing stimuli in Klf13(-/-) thymocytes is due in part to increased expression of BCL-X(L), a potent antiapoptotic factor. This finding was confirmed in splenocytes and total thymocytes by real-time quantitative PCR and Western blot as well as in CD4+CD8- single-positive thymocytes by real-time quantitative PCR. Furthermore, EMSA and luciferase reporter assays demonstrated that KLF13 binds to multiple sites within the Bcl-X(L) promoter and results in decreased Bcl-X(L) promoter activity, making KLF13 a negative regulator of BCL-X(L).

Author List

Zhou M, McPherson L, Feng D, Song A, Dong C, Lyu SC, Zhou L, Shi X, Ahn YT, Wang D, Clayberger C, Krensky AM

Author

Demin Wang PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Apoptosis
Cell Cycle Proteins
Cell Survival
Chemokine CCL5
Electrophoretic Mobility Shift Assay
Gene Expression Regulation
Kruppel-Like Transcription Factors
Lymphocyte Activation
Lymphoid Tissue
Mice
Mice, Knockout
Promoter Regions, Genetic
Repressor Proteins
T-Lymphocytes
bcl-X Protein
jenkins-FCD Prod-469 c3fc8ab87196149f9b23743c01b947d47e7319e5